Coatings for the manufacture and application of polyhydroxyalkanoate medical devices

ABSTRACT

Biocompatible coatings and spin finishes that can be applied to polyhydroxyalkanoate (PHA) polymers, and medical devices made from PHA polymers, have been developed. The coatings impart good lubricity to PHA polymers, particularly to fibers and braids made from these materials, making the coatings ideal for use on medical devices such as PHA braided sutures. The spin finishes can be applied to PHA fibers to facilitate their manufacture, and also for their conversion to other products, including medical textiles. The spin finishes serve to protect multifilament fiber bundles, and keep them intact following extrusion, and also to impart lubricity to the fiber bundles and monofilament fibers so that they are not damaged in subsequent processing steps particularly in textile processing. The coating reduces tissue drag of, for example, braided sutures.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims benefit of U.S. Provisional Application No.61/318,014, filed on Mar. 26, 2010; U.S. Provisional Application No.61/325,686, filed on Apr. 19, 2010; U.S. Provisional Application No.61/363,543, filed on Jul. 12, 2010; and U.S. Provisional Application No.61/411,629, filed on Nov. 9, 2010, all of which are hereby incorporatedherein by reference in their entirety.

FIELD OF THE INVENTION

The present invention generally relates to polymeric compositions thatcan be processed into fibers, and subsequently converted into textileconstructs such as knitted and woven meshes, braids, and vascular graftsusing continuous processes. The polymeric compositions include coatedpolyhydroxyalkanoate polymers and copolymers.

BACKGROUND OF THE INVENTION

There is a need for absorbable braided sutures with improvedperformance. In particular, these sutures should have high initialtensile strength, prolonged strength retention in vivo, good knotsecurity and tie down (with a small knot bundle), good handlingcharacteristics, and be biocompatible. The braided sutures should alsohave a low tissue drag that minimizes trauma to the sutured tissues.Biocompatible braided polyhydroxyalkanoate (“PHA”) sutures, or thosehaving a braided component, can be made with high tensile strength,prolonged strength retention in vivo, and good knot security; however,it would be advantageous if the tissue drag resulting from the braidedstructure of the suture could be reduced.

A number of different types of coatings have been applied to braidedsutures to lower tissue drag. These coatings must: impart good lubricityto the fiber/braid, have a reasonable shelf life, be biocompatible, andbe compatible with the physical and chemical structure of the fiber. Forexample, the coating must not react with the suture fiber, dissolve thefiber, or adversely alter the mechanical and thermal properties of thefiber. Thus, it is desirable to identify coatings that can be applied toPHA braided sutures to reduce tissue drag by imparting good lubricity tothe braid and fill the braid interstices without adversely altering theinherent properties of the fiber/braid. Moreover, it is particularlydesirable to identify coatings that can be applied to braided sutures,or sutures containing braided components, made from P4HB polymers andcopolymers thereof.

In addition to providing coatings for PHA fibers that reduce tissuedrag, it is desirable to identify spin finishes that can be applied toPHA fibers to facilitate their manufacture and, optionally, theirconversion to other products, including medical textiles. Spin finishesare applied during extrusion of multifilaments to keep the fiber bundleprotected and intact, and to impart lubricity to the fiber bundle sothat it may be manipulated in subsequent processing steps withoutdamaging the fiber. Spin finishes are also applied to monofilament tofacilitate textile processing without damaging the fiber. Spin finishesfor medical applications must satisfy a number of conditions. Theseinclude compatibility with the fiber (similar to that described forsuture coatings), and effectiveness under the process conditions, forexample, in processes such as spinning and orienting of the fiber, andin knitting or weaving of the fiber. In addition, it must be easy toapply the spin finish, and easy to remove the spin finish withoutdamaging the fiber or adversely impacting any component in the fibersuch as dye, using conditions that are compatible with the fiber'ssubsequent use in a medical device. Residues of the spin finish shouldalso be easily detectable, and any spin finish left on the device, evenresidues, needs to be biocompatible. The spin finish should also bestable with a long shelf life, and any spin finish left on the finalproduct should not adversely impact the properties or the shelf life ofthe final product.

It is also desirable to provide multifilament with a lower denier perfilament (dpf) and improved tenacity compared to uncoated multifilament.Such fibers can be used to prepare higher strength medical devices aswell as reduce the device profile.

It is an object of the present invention to provide methods to producecoated PHA braids for use as sutures and in other medical devices,wherein the coating provides the device with good lubricity to minimizetrauma to tissues, and good knot strength (in the case of a suture),without adversely impacting the properties of the PHA polymer.

It is a further object of the present invention to provide processes toproduce PHA multifilament fiber using spin finish, and process PHAmonofilament and multifilament fibers into other forms, such astextiles, with the aid of spin finish such that the fibers may beprocessed without damage, and the spin finish imparts lubricity to aidin the subsequent processing of the fiber.

It is another object of the present invention to provide coated PHAmultifilament and monofilament fibers, coated PHA braided sutures,coated PHA braided structures as components of other devices, and othercoated PHA medical devices and textiles, including monofilament andmultifilament knitted and woven meshes, and vascular grafts, which arebiocompatible and can be used in medical applications, for example, asimplants for soft tissue repair and reconstruction, temporary woundsupport, cosmetic, breast, facial, and plastic surgery, and for theregeneration and replacement of tissues. Such devices and textiles maybe further coated or encapsulated by or contain collagen.

It is yet another object of the invention to provide PHA multifilamentfibers with low filament denier and higher tenacity.

It is still another object of the invention to provide coatings and spinfinishes that can be used in processing PHA polymers to yield materialswith excellent physical and mechanical properties, and biocompatibility.

SUMMARY OF THE INVENTION

Biocompatible coatings and spin finishes that can be applied topolyhydroxyalkanoate (PHA) polymers, and medical devices made from PHApolymers, have been developed. The spin finishes can be applied to PHAfibers to facilitate their manufacture, and also for their conversion toother products, including medical textiles. The spin finishes protectthe multifilament fiber bundles, keeping them intact followingextrusion, and imparting lubricity to the fiber bundles and monofilamentfibers so that they are not damaged in subsequent processing steps,particularly in textile processing. In the preferred embodiment, thecoatings and spin finish are applied to a polyhydroxyalkanoate polymer,and in the most preferred embodiment, the PHA polymer comprises4-hydroxybutyrate. In a preferred embodiment, the coating or spin finishis a polymer or oligomer of an alkylene oxide, such as ethylene oxide orpropylene oxide, or a copolymer thereof.

The spin finish is preferably a liquid at the fiber processingtemperature. For example, if P4HB is processed at or near roomtemperature, the spin finish is preferably a liquid at room temperature.In other embodiments, the polyalkylene oxides can be wetted with wateror solvent to provide a liquid solution at the processing temperature. Aparticularly preferred embodiment is where the spin finish ispolyethylene glycol (PEG) with an average molecular weight ofapproximately 400 Daltons (PEG 400) to 2000 daltons (PEG 2000) appliedto a poly-4-hydroxybutyrate polymer or copolymer thereof. PEG with anaverage molecular weight of approximately 400 Daltons (PEG 400) to 1000daltons (PEG 1000) is preferred for PHAs being processed at or near roomtemperature. Higher molecular weights can be preferable for PHAs beingprocessed at higher temperatures.

In another preferred embodiment for the processing of monofilament PHAfibers into textiles, the spin finish is polyethylene glycol sorbitanmonolaurate (e.g., a polysorbate detergent available under the brandTween® 20). A particularly preferred embodiment is where the spinfinish, Tween® 20, is applied to monofilament PHA fiber and knitted orwoven into a textile construct, and the PHA fiber comprises4-hydroxybutyrate.

The preferred coating weight for a spin finish will depend on the fiberbeing processed. Monofilaments require less spin finish thanmultifilaments, due to the smaller total surface area of a monofilamentfiber. So a preferred coating weight on a monofilament may be less than2 wt %, preferably less than 1 wt %, while for multifilament it may beless than 10 wt %, preferably less than 8 wt %. Spin finishes can beremoved by a scouring process to prevent cytotoxicity. In preferredembodiments, the residual content of Tween® 20 after scouring is lessthan about 0.5 wt %, including less than about 0.4, 0.3, 0.2, 0.1, 0.09,0.08, 0.07, 0.06, 0.05, 0.04, or 0.03 wt %. In preferred embodiments,the residual content of PEG 400 after scouring is less than about 2 wt%, including less than about 1, 0.5, 0.4, 0.3, 0.2, or 0.1 wt %.

The textile construct produced from the coated PHA fibers may be furthercoated, impregnated, covered, or encapsulated by or contain collagen.

The coatings impart good lubricity to PHA polymers, particularly tofibers and braids made from these materials, making the coatings idealfor use on medical devices such as PHA braided sutures. Braidedmonofilament fibers or multifilament yarns are provided that are coatedwith polymers or oligomers of ethylene oxide, polymers or oligomers ofpropylene oxide, polyvinyl alcohol, or combinations thereof. Thesebraided fibers or yarns have an average tissue drag force at least 10%lower than the uncoated braid, including at least 20, 30, 40, 50, 60,70, 80, 90, 100% lower than the uncoated braid.

The polyhydroxyalkanoate of the braided fiber or yarn preferably has amolecular weight between 50,000 and 1,200,000. In preferred embodiments,the polyhydroxyalkanoate is 4-hydroxybutyrate.

In a preferred embodiment, the coating is polyethylene glycol (PEG) withan average molecular weight of approximately 1000 Daltons (PEG 1000) to10,000 daltons (PEG 10000) applied to devices, such as braided sutures,derived from poly-4-hydroxybutyrate or copolymers thereof.

In another embodiment, the coating is polyvinyl alcohol (PVOH). Aparticularly preferred embodiment is where the coating is polyvinylalcohol applied to a poly-4-hydroxybutyrate polymer or copolymer thereofor applied to devices, such as braided sutures, derived frompoly-4-hydroxybutyrate or copolymers thereof.

In preferred embodiments, the biocompatible coating is present on thePHA polymers or the medical devices made from PHA polymers in a coatingweight of about 0.1 wt % to 10 wt %, including about 0.1, 0.2, 0.3, 0.4,0.5, 0.6, 0.7, 0.8, 0.9, 1, 2, 3, 4, 5, 6, 7, 8, 9, and 10 wt %. Forexample, PEG2000 is preferably present on the PHA polymers or themedical devices made from PHA polymers in a coating weight of less than10 wt %, more preferably less than 7 wt %, even more preferably lessthan 5 wt %. For example, PVA is preferably present on the PHA polymersor the medical devices made from PHA polymers in a coating weight ofless than 6 wt %, more preferably less than 4 wt %, even more preferablyless than 3 wt %.

A method of reducing the tissue drag force of a braided suture formedfrom polyhydroxyalkanoate filaments is also provided. This method caninvolve coating the braided suture with polymers or oligomers ofethylene oxide, polymers or oligomers of propylene oxide, polyvinylalcohol, or combinations thereof.

DETAILED DESCRIPTION OF THE INVENTION I. Definitions

“Polyhydroxyalkanoates” or “PHAs” are linear polyesters produced innature by bacterial fermentation of sugar or lipids. Depending upon themicroorganism and the cultivation conditions, homo- or copolyesters withdifferent hydroxyalkanic acids are generated.

“Poly-4-hydroxybutyrate” as generally used herein means a homopolymercomprising 4-hydroxybutyrate units. It may be referred to herein as P4HBor TephaFLEX® biomaterial (manufactured by Tepha, Inc., Lexington,Mass.).

“Copolymers of poly-4-hydroxybutyrate” as generally used herein meansany polymer comprising 4-hydroxybutyrate with one or more differenthydroxyalkanic acid units.

“Blend” as generally used herein means a physical combination ofdifferent polymers, as opposed to a copolymer comprised of two or moredifferent monomers.

“Breast reconstruction devices” means devices for (i) breastaugmentation, including devices for use with breast implants (e.g.saline or silicone implants), (ii) mastopexy, (iii) breast reduction(including removal, reshaping and reorienting of breast tissue), and(iv) breast reconstruction following mastectomy with or without breastimplants.

“Tensile modulus” is the ratio of stress to strain for a given materialwithin its proportional limit.

“Toughness” means a property of a material by virtue of which it canabsorb energy; the actual work per unit volume or unit mass of materialthat is required to rupture it. Toughness is usually proportional to thearea under the load-elongation curve such as the tensile stress-straincurve. (Rosato's Plastics Encyclopedia and Dictionary, Oxford Univ.Press, 1993)

“Elongation” or “extensibility” of a material means the amount ofincrease in length resulting from, as an example, the tension to break aspecimen. It is expressed usually as a percentage of the originallength. (Rosato's Plastics Encyclopedia and Dictionary, Oxford Univ.Press, 1993).

“Molecular weight” as used herein, unless otherwise specified, refers tothe weight average molecular weight (Mw), not number average molecularweight (Mn), and is measured by gel permeation chromatography (GPC)relative to polystyrene.

“Absorbable” as generally used herein means the material is broken downin the body and eventually eliminated from the body within five years.

“Biocompatible” as generally used herein means the biological responseto the material or device being appropriate for the device's intendedapplication in vivo. Any metabolites of these materials should also bebiocompatible.

“Cytotoxicity” refers to the harmful affect of a medical device on cellsas set forth in ISO 10993-5. Cytotoxicity can be measured using a rapid,standardized test that is very sensitive and inexpensive. These testscan determine if the materials in a medical device contain significantquantities of harmful extractables that negatively effect cellularcomponents. Testing is required for all types of medical devices. Anagar overlay media can be placed on top of a monolayer of L-929 cells,and a sample is placed on top of the agar media, then incubated. For MEMelution, an extract of the sample in Minimum Essential Medium (MEM) isplaced in contact with the monolayer of L-929 cells and then incubated.In both methods the cells are scored for cytotoxic effect.

“Spin finishes” are lubricants and antistatic agents that are applied totextile fibers and yarns during production and processing.

“Denier” is a unit of weight of fiber or yarn. The weight in grams of9,000 meters of fiber or yarn is its denier.

“Tenacity” is the strength of a yarn or fiber for its given size. It maybe defined as the grams of breaking force per denier or breakingstrength (grams force) divided by denier (i.e. grams per denier, orgpd).

“Pick count” is defined as the number of crossovers of sheath yarns perlinear inch of suture or braid.

“PPI” stands for picks per inch.

“TPI” stands for twists per inch.

“Lubricity” is the measure of the reduction in friction by a lubricant.Lubricity of a material cannot be directly measured, so tests areperformed to quantify a lubricant's performance. This is done bydetermining how much wear is caused to a surface by a givenfriction-inducing object in a given amount of time. For sutures,lubricity can be determined by measuring tissue drag. A monofilament haslow tissue drag, meaning it passes smoothly through tissue. Braided ortwisted sutures have higher tissue drag, but are easier to knot and havegreater knot strength. Braided sutures can be coated to increaselubricity and lower tissue drag.

II. Compositions

Methods have been developed to produce lubricious compositions of PHApolymers that are suitable for the manufacture of PHA fibers and yarns,and for the manufacture of medical devices and medical devicecomponents, as well as to improve the lubricity of certain medicaldevices, such as sutures comprising PHA braided structures Multifilamentyarn comprising polyhydroxyalkanoate polymer has a denier per filamentof less than 4.0. The multifilament yarn has a tenacity greater than 6.1grams per denier. These methods have been applied to P4HB multifilamentsprepared by melt processing, and to P4HB multifilaments andmonofilaments braided, woven or knitted into medical device products,such as braided sutures and surgical meshes.

A. Polymers

The processes described herein can typically be used to apply coatingsor spin finishes to polyhydroxyalkanoate polymers, and more preferablyto poly-4-hydroxybutyrate (P4HB) or a copolymer thereof. Copolymersinclude P4HB with 3-hydroxybutyrate, and P4HB with glycolic acidmonomer. P4HB and copolymers thereof can be obtained from Tepha, Inc. ofLexington, Mass. Preferred PHA polymers have a weight average molecularweight (Mw) suitable for melt processing, and more preferably a Mw of50,000 to 1,200,000, and even more preferably 100,000 to 800,000 basedon gel permeation chromatography (GPC) relative to polystyrenestandards. If desired, the PHA polymer may be blended with another PHApolymer prior to melt extrusion of the fibers, or blended with a non-PHAmaterial, including other absorbable biocompatible polymers, dyes andactive agents (such as drug molecules or other therapeutic, prophylacticor diagnostic agents).

Poly-4-hydroxybutyrate (P4HB) and copolymers thereof can be producedusing transgenic fermentation methods, see, for example, U.S. Pat. No.6,548,569 to Williams et al., and are produced commercially, forexample, by Tepha, Inc. (Lexington, Mass.). Poly-4-hydroxybutyrate(P4HB, TephaFLEX® biomaterial) is a strong, pliable thermoplasticpolyester that, despite its biosynthetic route, has a relatively simplestructure

The polymer belongs to a larger class of materials calledpolyhydroxyalkanoates (PHAs) that are produced by numerousmicroorganisms (see, for example, Steinbüchel A., et al. Diversity ofBacterial Polyhydroxyalkanoic Acids, FEMS Microbial. Lett. 128:219-228(1995)). In nature these polyesters are produced as storage granulesinside cells, and serve to regulate energy metabolism. They are also ofcommercial interest because of their thermoplastic properties, andrelative ease of production. Several biosynthetic routes are currentlyknown to produce P4HB:

This schematic shows some of the known biosynthetic pathways for theproduction of P4HB. Pathway enzymes are: 1. Succinic semialdehydedehydrogenase, 2. 4-hydroxybutyrate dehydrogenase, 3. dioloxidoreductase, 4. aldehyde dehydrogenase, 5. Coenzyme A transferase and6. PHA synthetase.

Chemical synthesis of P4HB has been attempted, but it has beenimpossible to produce the polymer with a sufficiently high molecularweight that is necessary for most applications (Hori, Y., et al.,Polymer 36:4703-4705 (1995)).

U.S. Pat. Nos. 6,245,537, 6,623,748 and 7,244,442 describe methods ofmaking PHAs with little endotoxin, which is suitable for medicalapplications. U.S. Pat. Nos. 6,548,569, 6,838,493, 6,867,247, 7,268,205,and 7,179,883 describe use of PHAs to make medical devices. Copolymersof P4HB include 4-hydroxybutyrate copolymerized with 3-hydroxybutyrateor glycolic acid (U.S. patent application No. 20030211131 by Martin andSkraly, U.S. Pat. No. 6,316,262 to Huisman, et al., and U.S. Pat. No.6,323,010 to Skraly, et al.). Methods to control molecular weight of PHApolymers have been disclosed by U.S. Pat. No. 5,811,272 to Snell, et al.

PHAs with controlled degradation and degradation in vivo of less thanone year are disclosed in U.S. Pat. Nos. 6,548,569, 6,610,764,6,828,357, 6,867,248, and 6,878,758 to Williams, et al. and WO 99/32536to Martin, et al. Applications of P4HB have been reviewed in Williams,S. F., et al., Polyesters, III, 4:91-127 (2002), and by Martin, D., etal. Medical Applications of Poly-4-hydroxybutyrate: A Strong FlexibleAbsorbable Biomaterial, Biochem. Eng. J. 16:97-105 (2003). The latterreference also describes monofilament fibers and textiles of P4HB.Medical devices and applications of P4HB have also been disclosed by WO00/56376 to Williams, et al. Several patents including U.S. Pat. Nos.6,555,123, 6,585,994, and 7,025,980 to Williams, et al. describe the useof PHAs in tissue repair and engineering.

WO 04/101002 to Martin, et al. discloses monofilament and multifilamentfibers, and knitted meshes of P4HB produced by knitting these fibers.

WO 06/015276 to Rizk, et al. discloses non-curling P4HB fibers for useas sutures, and other medical devices including surgical meshes.

WO 07/003,185 to Coleman, et al. discloses interposition andaugmentation devices for tendon and ligament repair comprising P4HBfibers, and P4HB multifilament fiber with a filament denier of 4.4 andtenacity of 6.04 gram/denier.

B. Coatings and Spin Finishes

The processes described herein typically use polymers or oligomers ofethylene oxide or propylene oxide as the spin finish and coatingmaterials. The coating material can also be, for example, polyvinylalcohol. For the textile processing of PHA monofilament fibers, the spinfinish may be Tween® 20, a polyoxyethylene derivative of sorbitanmonolaurate.

Preferred polymers or oligomers of ethylene oxide and propylene oxidefor textile processing have relatively low molecular weights, lowtoxicity, good solubility in water and alcohols, can be easily detected,can be easily removed from the PHA polymer preferably using water, andcan be formulated so that they can be readily applied to PHA polymerspreferably by an application process that employs a pump. The preferredpolymers or oligomers of ethylene oxide and propylene oxide should alsobe compatible (non-absorbable and non-reactive) with the PHA polymers,as well as impart and maintain lubricity to the PHA polymer. The spinfinish and coatings should not readily leave the PHA polymer surfaceduring processing unless in a scouring process specifically designed toremove them.

A preferred polymer of ethylene oxide is polyethylene glycol having anaverage molecular weight of approximately 400 to 10,000 daltons (e.g.,PEG 400, PEG 2000, and PEG 10000), most preferably 1000 to 10,000,depending on whether the polymer is being used as a spin finish fortextile processing or a coating to reduce tissue drag of a device, suchas a suture. PEG 400 passed cytotoxicity testing at a coating weight of4.8 wt %. Polyethylene glycols manufactured by Spectrum ChemicalManufacturing Corporation are available under the tradename CARBOWAX. Inaddition, blends of the above-mentioned polymers and oligomers can beused as spin finish and coating materials.

Polyvinyl alcohol (“PVA”) can also be used as a coating. Preferredcoating weights for PVA range from 0.1 to 6%, preferably less than 3 wt%.

C. Other Components

The PHA polymers and copolymers may contain other materials, includingplasticizers, nucleants, other polymers (including absorbable polymers),additives, dyes, and compatibilizers. Examples of plasticizers aredisclosed by U.S. Pat. No. 6,905,987 to Noda et al. Other components maybe added to impart benefits such as, but not limited to, increasedstability, including oxidative stability, brightness, color,flexibility, resiliency, workability, processibility (by addition ofprocessing aids), and viscosity modifiers. Other absorbable polymersthat may be included in the compositions include those comprising thefollowing monomers: glycolic acid, lactic acid, trimethylene carbonate,p-dioxanone, and caprolactone.

Active components, including therapeutic, diagnostic and/or prophylacticagents, or other substances may be incorporated into the PHA polymersand copolymers, either at the time of extrusion, or in a laterprocessing step, particularly as a coating. Such compositions may beused for controlled release of the drugs or other substances. These maybe proteins, peptides, sugars, polysaccharides, glycoproteins, lipids,lipoproteins, nucleic acid molecules, inorganic or organic syntheticmolecules, or combinations thereof. It may also be advantageous toincorporate contrast agents, radiopaque markers, or radioactivesubstances.

A particularly preferred coating is collagen, which exhibits excellentcell adhesion properties, promotes natural wound healing, and stimulatesfibroblast adhesion and growth. In particular, collagen coated on PHAfabrics can promote incorporation of the device into tissue structures,and therefore it can be particularly desirable to apply collagen to thesurfaces of PHA devices and even to entirely cover or encapsulate thedevice with collagen.

For certain applications it may also be desirable to incorporatefillers, including materials such as, but not limited to, titaniumdioxide, calcium carbonate, hydroxyapatite, and tricalcium phosphate.

III. PHA Medical Devices and Methods of Manufacturing

A. Fibers and Textiles for Making PHA Medical Devices

In a preferred embodiment, PHA multifilament can be prepared with adenier per filament (dpf) of less than 4, and even more preferably lessthan 3 dpf. It has been discovered that P4HB multifilament can beprepared with a dpf of approximately 2. It has also been discovered thatP4HB multifilament can be prepared with a tenacity of greater than 6.5.Application of polymers and oligomers of ethylene and propylene oxide tothe multifilament extrudate protects the extruded fiber bundle, andkeeps the fiber bundle intact so that the individual fibers are notseparated and damaged. The spin coating remains stable on the P4HBmultifilament even as the yarn is moving. It has also been discoveredthat polymers and oligomers of ethylene or propylene oxide impart goodlubricity to the PHA polymers, and can be pumped during the manufactureof the fibers under the conditions required for extrusion of themultifilament. In an even more preferred embodiment, P4HB multifilamentfibers are coated with PEG400.

Polymers and oligomers of ethylene or propylene oxide may also beapplied to other fibers of PHA polymers and copolymers to aid insubsequent processing. In a preferred embodiment, polymers and oligomersof ethylene oxide are applied to P4HB monofilament fibers. In an evenmore preferred embodiment, PEG400 is applied to P4HB monofilament fibersprior to further processing.

In addition to using polymers or oligomers of ethylene or propyleneoxide to process PHA monofilament into textile products, such assurgical meshes, it has been discovered that Tween® 20 may also be usedfor this purpose. In a preferred embodiment, Tween® 20 is applied toP4HB monofilament fibers prior to further processing.

It has been found that PHA polymers and copolymers coated with polymersand oligomers of ethylene or propylene oxide can be readily convertedinto medical device products, particularly products containing textilessuch as braided sutures, monofilament and multifilament meshes, smalltubes (including vascular grafts), and other knitted and woven devices.Use of polymers and oligomers of ethylene or propylene oxide as spinfinishes minimize damage to the fibers during processing. In contrast,PHA fibers processed without spin finish can be severely damaged insubsequent processing steps.

It has also been found that polymers and oligomers of ethylene oxide canbe left on the PHA polymers without adversely altering the properties ofthe polymer and the device. Long term exposure to these spinfinishes/coatings does not significantly alter the mechanical propertiesor molecular weight (Mw) of the fibers. This is important particularlyif there is a significant time period between, for example, themanufacture of the multifilament and its subsequent processing into atextile construct.

It has also been discovered that Tween® 20 can be used as a spin finishon PHA monofilament fibers that are used to produce medical deviceproducts, particularly those produced by knitting and weaving processes(such as monofilament surgical mesh devices). Use of Tween® 20 onmonofilament PHA fibers as a spin finish minimizes damage to the fibersduring processing.

In most cases it is necessary to remove substantially all the spinfinish from a medical device prior to its use. Spin finishes have atendency to attract particulate to the surface they adhere to, andtherefore removal of the spin finish is desirable in most instances.High levels of certain spin finishes can also be too toxic for medicaldevice use, and in these cases removal to a non-toxic level is essential(otherwise the spin finish cannot be used). It should be noted that somePHA polymers, including P4HB polymers and copolymers thereof, haverelatively low melting points that significantly limit conditions underwhich spin finishes can be applied and removed. For example, exposure tohigh temperatures will melt the PHA fibers or cause changes in thephysical (e.g. mechanical and morphological) properties of the polymers.Thus, spin finishes that are applied or removed at high temperaturescannot be used. Furthermore, the PHA polymers are also degradable, andtherefore susceptible to hydrolysis under certain conditions, and aresoluble in a range of solvents. These PHA properties also limit thechoice of available spin finishes (e.g. some solvents used to apply orremove spin finish will dissolve the P4HB). As will be apparent to oneskilled in the art, selection of a spin finish for a PHA polymer orcopolymer is a complicated task with the spin finish needing to satisfya large number of performance requirements not just in processing butalso in the removal process.

In a preferred embodiment, it has been found that polymers and oligomersof ethylene and propylene oxide can be substantially removed from PHApolymers and copolymers after product fabrication without damaging theproperties of the PHA polymers or the PHA fibers, and that the resultingscoured products pass cytotoxicity testing. Notably, certain other spinfinishes tested, for example, DacoSpin®, failed cytotoxicity testingunder the same conditions with P4HB multifilament braided sutures. In apreferred embodiment, devices of PHA polymers and copolymers treatedwith polymers and oligomers of ethylene and propylene oxide are scouredwith water to remove the spin finish. These devices may also be washedwith alcohol as an alternative, or additional, scouring process, tofurther reduce the level of spin finish remaining on the device. In aparticularly preferred embodiment, devices comprising P4HB fibers coatedwith PEG400 are scoured with water, and optionally rinsed with analcohol solution.

In another preferred embodiment, it has been found that Tween® 20 canalso be applied to PHA monofilament fibers as a spin finish and besubstantially removed from PHA polymers and copolymers after productfabrication without damaging the properties of the PHA polymers or thePHA monofilament fibers, and that the resulting scoured products passcytotoxicity testing.

Fibers derived from PHA polymers and copolymers coated with polymers andoligomers of ethylene and propylene oxide as spin finish, and fibersderived from PHA monofilament coated with Tween® 20 as spin finish,possess properties that are desirable in preparing medical products,particularly implantable medical devices. For example, these fibers maybe used to make partially or fully absorbable biocompatible medicaldevices, or components thereof. Such devices may include, but are notlimited to: stent, stent graft, drug delivery device, device fortemporary wound or tissue support, device for soft tissue repair,devices for cosmetic, neck and plastic surgery, replacement orregeneration (including facial surgery procedures such asblepharoplasty, facial scar revisions, forehead lifts (brow lifts),mentoplasty, malar augmentation, otoplasty, rhinoplasty, neck liftsurgery, threadlifts (to lift and support sagging areas of the face,brow and neck), and rhytidectomy), repair patches including hybridmeshes, tissue engineering scaffolds, retention membranes (for example,to retain bone graft), anti-adhesion membrane, tissue separationmembrane, hernia repair device, breast reconstruction device, devicecoating (including devices to improve fixation), cardiovascular patch,vascular closure device, vascular graft, sling, biocompatible coating,rotator cuff repair device, meniscus repair device, adhesion barrier,guided tissue repair/regeneration device, articular cartilage repairdevice, nerve guide, tendon repair device, ligament repair device,intracardiac septal defect repair device, including but not limited toatrial septal defect repair devices and PFO closure devices, left atrialappendage (LAA) closure device, pericardial patch, bulking and fillingagent, vein valve, heart valve, bone marrow scaffold, meniscusregeneration device, ligament and tendon graft, ocular cell implant,spinal fusion device, imaging device, skin substitute, dural substitute,bone graft substitute, wound dressing, and hemostat.

B. Methods of Making PHA Multifilament Yarn Coated with Spin Finish

In a preferred method, bulk PHA resin in pellet form is dried to under300 ppm of water using a rotary vane vacuum pump system. The dried resinis transferred to a feed hopper with a nitrogen purge to keep thepellets dry. The pellets are gravity fed into a chilled feeder section,and introduced into an extruder barrel, for example, 0.75 inches indiameter and 25.69 inches long via an extrusion screw with 30:1 L/Dratio. A preferred extruder barrel contains four heating or extrusionzones and is manufactured by American Kuhne. The heated and softenedresin from the extruder is fed into a heated metering pump (melt pump)and from the melt pump the extruded resin is fed into the heated block.The spin head houses a spin pack comprising filtering media (screens)and spinnerets containing the desired number of holes for forming theindividual filaments of the yarn. (For example, 15, 30 and 60 or moreholes.) The extruded filaments exit the spinneret, pass through a hotchimney, and are then air-cooled until they solidify inside a contained,clear tube. The resulting yarn is then passed through a spin finishapplicator, over two rotating godets, and is collected on a precisionwinder as the yarn exits the second godet. The denier of the yarn atthis point can range significantly depending on the number of holes andspeed of the godets. A preferred range is 120-840 denier. The quantityof spin finish applied to the filaments during passage through the spinfinish applicator may be controlled by varying the concentration of thespin finish while keeping all other parameters constant. This alsoallows direct comparison between spin finishes. In a preferred method,orientation of the yarn is accomplished offline, although it can also bedone inline. In a preferred method, the extrudate is collected ontospools and then three sets of paired godets are used to orient the yarnfrom a payoff system holding the extrudate collection spool. Theextruded yarn is rewet via a controlled pump speed spin finishapplicator. In a preferred method, the yarn is hot stretched.

In another preferred method, the PHA multifilament has a denier perfilament of less than 4, and more preferably less than 3.

In a particularly preferred method, the PHA polymer is P4HB with aweight average molecular weight of 100,000-800,000, and the spin finishis PEG400.

C. Method of Making Braided PHA Multifilament Sutures

In a preferred method, drawn 60-filament yarn coated with spin finish isformed into braided sutures as follows. PHA yarn is twisted and/or pliedand wound onto bobbins. These bobbins are then placed on 8, 12 or16-carrier braiders and braided at various picks per inch. For someconstructions, cores are made and put in the center of the braid, forexample, 60-filament yarn, multiple plied yarn strands, or monofilamentfibers.

In the preferred method, braided sutures are manufactured from yarnscomprising 4-hydroxybutyrate that are produced from P4HB polymers andcopolymers with a weight average molecular weight between 100,000 and800,000. The braided sutures have a tenacity from about 3-8 grams perdenier, a percent elongation to break of less than 50 percent, and adenier per filament from 0.1 to 8.0. The braids are preferably made fromyarns that are oriented to about 1.4 to 3.1 denier per filament (dpf).In one embodiment, yarns comprising 4-hydroxybutyrate can be braidedinto sutures using conventional or spiroid braid constructions as shownin Table 1.

TABLE 1 4-hydroxybutyrate yarns USP Approx Size Diam. mm Approx DenierUSP Size Diam. mm Denier 3.0-5.0 >0.600 >3600 3/0 0.20-0.249 800   2.00.50-0.599 3500 4/0 0.15-0.199 600 1 0.40-0.499 2500 5/0 0.10-0.149 4000 0.35-0.399 1700 6/0 0.070-0.099  200 2/0 0.30-0.399 1200 7/00.050-0.069  <100

D. Scouring of PHA Devices and Fibers to Remove Spin Finish

In a preferred method, spin finish is removed from PHA fibers anddevices by scouring with water. The PHA material is washed in a waterbath, using cold water—typically between 4° C. and ambient temperature(i.e., water sufficiently cold that it does not adversely alter theproperties of the PHA material, such as where the PHA has a low meltingtemperature). After washing for a pre-determined time, for example, fiveminutes or more, the PHA material is rinsed with fresh water. In thepreferred method, a water-soluble detergent, such as Tween 20 or Tween80, may also be added to the water at 1 to 10,000 ppm to facilitatescouring of the PHA material, and then the PHA material is carefullyrinsed to remove the detergent. Placing the samples in an ultrasonicbath for a predefined period of time, for example, from 1 second up to24 hours or 48 hours, can also be used to achieve enhanced scouring ofthe PHA material in water. As an alternative to adding detergent to thewater, the PHA materials may also be scoured with aqueous solutions ofalcohol, for example, ethanol or isopropylalcohol, and if desired,combining this treatment with ultrasonic cleaning. Alternatively, thePHA fibers and devices may be washed with alcohol solutions afterscouring with water. Once the PHA fibers and devices have been scoured,the materials may be allowed to dry at ambient, or more preferably driedunder vacuum to remove residual moisture/solvent. It will be apparent tothose skilled in the art that various combinations of washing steps canbe used to scour the PHA fibers and devices.

E. Method of Coating PHA Devices with Collagen

In a preferred method, devices prepared from PHA polymers, including PHAsutures, meshes, and other textile constructs, are coated with collagen.The coating may range from a thin coating for example on the surface ofa PHA fiber to the complete coverage or encapsulation of a PHA device,such as a mesh, by collagen. A particularly preferred method involvescompletely encapsulating a mesh such that the device is effectively acollagen sponge reinforced with a PHA mesh. Such PHA reinforced collagensponges or coated devices can have the following desirable properties:good handling characteristics; absorb tissue exudate; prevent, reduce ordelay contracture of the wound; improve suture holding; conform well tothe wound or surgical site; provide a superior cosmetic repair, preventleakage; and facilitate tissue in-growth and a strong repair.

In a preferred method, PHA devices, particularly collagen spongesreinforced with PHA fabrics, can be prepared by immersing the PHA devicein an acid-swollen collagen suspension that has been blended into aslurry. For example, the monofilament mesh of Example 8, may be coatedwith collagen in this manner. After immersion, the coated device may beair-dried or freeze-dried, and if necessary the process repeatedmultiple times to build up the thickness of the coating. In a preferredmethod, the process is repeated until the entire PHA device isencapsulated in a collagen sponge. Alkali and neutral slurries ofcollagen may also be used (as well as collagen compositions that havebeen pre-digested with pepsin to remove the nonhelical terminal regionsof the collagen molecule). Generally, freeze drying is preferred when itis desirable to obtain a porous collagen coating or sponge, and porositycan be tailored, for example, by altering the concentration of thecollagen in the slurry. In a particularly preferred method, the averageporosity of the device is controlled to optimize the invasion of hostfibroblasts in vivo, and is at least 5 μm in diameter, and mostpreferably in the range of 5-150 μm. In a preferred method, the coateddevice may be pressed, molded or cut to the desired device shape.

In order to improve the adhesion of collagen to the PHA polymer, the PHApolymer may be modified prior to coating with collagen. A preferredmethod is modification by treatment with plasma. In a particularlypreferred plasma treatment, ammonia gas is used to produce a PHA polymersurface rich in amine groups. Plasma modified PHA surfaces may becoated, or crosslinked, and can have an increased affinity to bindcollagen.

In certain cases it is desirable to crosslink the collagen after coatingof a PHA device. Crosslinking can increase the tensile strength of thedevice, and improve the integrity of the coating and the handling of thedevice. Crosslinking can also be used to control the rate of in vivodegradation, and tailor the rate to the application. For example,crosslinking can be used to slow down the degradation of a PHAreinforced collagen sponge in order to allow the implanted collagen tobe replaced by host collagen. This can be particularly important wheretissue reinforcement or regeneration is necessary, for example, inhernia repair and rotator cuff repair procedures, and where a strongrepair is necessary.

A number of methods can be used to crosslink the collagen of a collagencoated PHA device. These include the formation of ionic bonds, covalentbonds, and hydrogen bonds. In a preferred method, the carboxyl groups ofaspartic and glutamic residues or the epsilon-amino acid groups oflysine and hydroxylysine are crosslinked. The amino side-chain groups ofasparagine and glutamine may also be crosslinked, and less preferablythe hydroxyl groups of serine, threonine and hydroxyproline. In apreferred method, the collagen is covalently crosslinked with aldehydesmost preferably formaldehyde, glutaraldehyde, glyceraldehyde, glyoxal,acetaldehyde, acrolein, and dialdehyde starch. The collagen may also becrosslinked with reagents such as carbodiimides, acyl azides, andisocyanates (e.g. 1,6-diisocyanatohexane). The degree of crosslinkingcan be altered, for example, by varying the concentration ofcrosslinking agent, and reaction time. In another preferred method, thecollagen is ionically crosslinked with trivalent metals, preferablychromium or aluminum. In yet another method, the collagen may becrosslinked with borohydrides (e.g. sodium or potassium borohydride). Inyet still another method, the collagen may be crosslinked by exposure toUV or other sources of irradiation. In one preferred embodiment, thecollagen is crosslinked by UV light at 120 μW/cm². In a less preferredmethod, the collagen may be crosslinked by heating preferably undervacuum. In the preferred method, the collagen is crosslinked aftercoating of the PHA device, however, the collagen may alternatively becrosslinked prior to coating.

The degree of crosslinking may also be controlled by derivatization ofthe collagen side groups prior to crosslinking, for example, bymethylation, acetylation or esterification. This method may also be usedto further modify the device properties.

The collagen coated PHA devices may further comprise other materials.These materials may be added to control the device degradation rate, addor enhance other properties. For example, collagen sponges reinforced byPHA meshes can carry active agents such as antibiotics, or othermaterials such as hyaluronic acid and fibronectin. Such compounds couldbe used to increase fibroblast proliferation and improve organizedtissue repair. A preferred method incorporates up to 5% hyaluronic acid(based on collagen weight). Another preferred method incorporates up to20% chondroitin sulfate. The latter may enhance cellular attachment.Plasticizers may also be added, for example, to improve flexibility andoptimize porosity. Preferred plasticizers are biocompatible andabsorbable, and include sorbitol, glycerine, and citrate.

In a preferred method, the collagen may also be further derivatized toalter its biological activity. In a preferred method, heparin is boundto the collagen to create non-thrombogenic surfaces.

The collagen coated PHA devices are preferably sterilized by ethyleneoxide or irradiation, most preferably at 2.5 to 10 millirad.

F. Fabrication of PHA Breast Reconstruction Devices

PHA polymers and copolymers possess properties that are desirable forpreparing devices for use in breast reconstruction, cosmetic surgery,facial and neck surgery. In a preferred method, PHA fibers are convertedinto breast reconstruction devices. In a particularly preferred method,PHA fibers are converted into meshes for breast reconstruction.Preferably, these meshes permit some fibrous tissue to grow into andaround the mesh to reinforce it, have initial strength and stiffness toprovide support, and yet are soft, supple, and barely palpable uponimplantation. Importantly, the meshes are sufficiently soft to preventrippling of the mesh during palpation of the breast. In an even morepreferred method, PHA fibers are woven into three-dimensional shapes foruse as breast reconstruction devices. Particularly preferred designs arethe BREFORM™ internal bra systems used for mastopexy, and manufacturedby Aspide Médical, La Talaudiere, France, and sling-shaped devicesdesigned to support the breast or a breast implant, as described forexample by U.S. Pat. No. 7,476,249 to Frank, US Patent Application No.2010/0137679 to Lashinski et al., and U.S. Pat. No. 7,670,372 to Shfaramet al., and the mesh breast implant support device described by USPatent Application No. 2009/0082864 to Chen. The PHA meshes may bederived from PHA monofilament, PHA multifilament, or combinations ofthese constructs. The mesh devices may also be hybrid structures, forexample, comprising PHA fibers and polypropylene and/or polyesterfibers. In a further embodiment, the PHA fibers may be used assuspension members and support elements for breast reconstruction asdescribed by US Patent Application No. 2008/0082113 to Bishop, and USPatent Application No. 2009/0248071 to Saint et al.

G. Coating Braided Sutures to Reduce Tissue Drag

Braided or twisted sutures have higher tissue drag (i.e., force requiredto pull the suture through tissue), but are easier to knot and havegreater knot strength. The disclosed coatings impart good lubricity toPHA polymers, particularly to fibers and braids made from thesematerials, making the coatings ideal for use on medical devices such asPHA braided sutures. Therefore, braided or twisted PHA sutures arepreferably coated with polymers or oligomers of ethylene oxide, polymersor oligomers of propylene oxide, polyvinyl alcohol, or combinationsthereof. These braided or twisted PHA sutures have an average tissuedrag force at least 10% lower than the uncoated braid, including atleast 20, 30, 40, 50, 60, 70, 80, 90, 100% lower than the uncoatedbraid.=

In a preferred embodiment, the coating is polyethylene glycol (PEG) withan average molecular weight of approximately 1000 Daltons (PEG 1000) to10,000 daltons (PEG 10000). In another embodiment, the coating ispolyvinyl alcohol (PVOH). A particularly preferred embodiment is wherethe coating is polyvinyl alcohol.

In preferred embodiments, the biocompatible coating is present on thetwisted or braided PHA sutures in a coating weight of about 0.1 wt % to10 wt %, including about 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1,2, 3, 4, 5, 6, 7, 8, 9, and 10 wt %. For example, PEG2000 is preferablypresent on twisted or braided PHA sutures in a coating weight of lessthan 10 wt %, more preferably less than 7 wt %, even more preferablyless than 5 wt %. For example, PVA is preferably present on the twistedor braided PHA sutures in a coating weight of less than 6 wt %, morepreferably less than 4 wt %, even more preferably less than 3 wt %.

The present invention will be further understood by reference to thefollowing non-limiting example.

Example 1 Preparation of P4HB Multifilament Coated with Spin Finish

P4HB (Tepha, Inc., Lexington, Mass.) (Mw 200-600K) was extruded intoP4HB multifilament as described in Section II.A (Method of Making PHAMultifilament Coated with Spin Finish) using the extruder operatingconditions set forth in Table 2, and spinnerets with 15, 30 and 60holes.

TABLE 2 Extruder Operating Conditions for P4HB Multifilament Feed 1 2 34 15° C. ± 10° C. 75° C. ± 40° C. 180° C. ± 50° C. 215° C. ± 40° C. 250°C. ± 40° C. Extruder Pump Block Spinneret Chimney RPM 230° C. ± 30° C.230° C. ± 30° C. 230° C. ± 30° C. 110° C. ± 60° C. 1 ± 1 Take UpPressure Melt G1 MPM G2 MPM SF RPM In Out Pump RMP 10 ± 10 10 ± 11 5 ± 51400 ± 80 600 ± 400 16 ± 9

The P4HB yarn extrudate was oriented offline using 3 sets of pairedgodets as described in Section II.A using the conditions for orientationset forth in Table 3.

TABLE 3 Orientation Conditions for P4HB Multifilament Speed (MPM) RollTemperature (° C.) GP 1 GP 2 GP 3 GP 1 GP 2 GP 3 10 60 ± 20 60 ± 20Ambient 56 ± 10 40 ± 10

Multiple extrusion runs were undertaken with different spin finishes,and different concentrations of spin finish in order to identify thosespin finishes that could be readily applied as a neat spin finish or asa solution in a compatible solvent preferably in liquid form, and wouldprovide good lubricity, protect the fiber bundle and keep it intact, inaddition to providing samples for biocompatibility testing, testing intextile manufacturing processes, and in scouring processes. The spinfinish or solution thereof would preferably have a viscosity in therange of 1 to 500,000 cP. The following spin finishes were evaluated:Dacospin® (Pulcra Chemicals), Lurol (Goulston Technologies), PEG400(Spectrum Chemical), PEG40 Stearate, Tween 20 (Uniqema), propyleneglycol (Alfa Aesar), Filapan® (Dystar), and Glycerin (PTI ProcessChemicals).

A 50% aqueous solution of glycerin was selected and evaluated based onlubricity. However, combination with the P4HB multifilament fiberprovided a very sticky product that was too difficult to process, and athigher concentrations resulted in fiber breakage during orientation.

Although the viscosity of Tween® 20 without dilution was found to be toohigh to allow consistent pumping, concentrations of 10, 25 and 50% inwater or ethanol could be applied to the fiber during extrusion, andconcentrations of 1% and 10% were applied during orientation. Duringorientation, Tween® 20 was found to be effective at keeping the fiberbundle intact.

Lurol was successfully applied to the P4HB yarn at concentrations of 10,and 50%, however, the fiber bundle did not stay intact when paying offonto the orientation line, and many broken filaments were observed.

PEG400 was applied to the P4HB yarn at concentrations of 10, 25 and 50%,and at a 1% concentration for orientation. This spin finish displayedideal properties by providing good lubricity, keeping the fiber bundleintact, and allowing easy payoff during orientation. Visual inspectionunder a microscope with a 10× magnification confirmed that the lubricantwas spread throughout the fiber.

PEG40 Stearate was found to be too viscous at high concentrations, andtherefore was evaluated at 10 and 15% concentrations for extrusion, and1% for orientation. At these concentrations, the fiber bundle did notremain completely intact.

Dacospin® concentrations of 5, 10 and 25% were evaluated for theextrudate, and a 1% concentration was applied during orientation. Atlower concentrations, the fiber bundle was found to separate, but thisproblem did not persist at the higher concentrations.

Propylene glycol was evaluated at concentrations of 25, 50 and 100%. Itcould be easily applied to the yarn, however, the fiber bundle tended toseparate during orientation even at higher concentrations.

Filapan® performed well during extrusion and orientation steps at a 25%concentration, and imparted good lubricity to the yarn.

Mechanical properties of oriented P4HB yarn produced using a spinneretwith 15 holes and PEG400 as spin finish are shown in Table 4.

TABLE 4 Mechanical properties of 15 Filament Oriented P4HB MultifilamentProduced with PEG400 as Spin Finish Denier per Break # Total filamentTenacity Elongation Specimen # Filaments Denier (dpf) (gpd) (%) 1 15 322.13 7.394 18.2 2 15 32 2.13 8.081 19.6 Average 15 32 2.13 7.738 18.9

Mechanical properties of oriented P4HB yarn produced using a spinneretwith 30 holes and PEG400 as spin finish are shown in Table 5.

TABLE 5 Mechanical properties of 30 Filament Oriented P4HB MultifilamentProduced with PEG400 as Spin Finish Denier per Break # Total filamentTenacity Elongation Specimen # Filaments Denier (dpf) (gpd) (%) 1 30 682.27 7.232 20.4 2 30 68 2.27 7.569 16.0 3 30 68 2.27 7.617 18.8 Average30 68 2.27 7.473 18.4

Mechanical properties of oriented P4HB yarn produced using a spinneretwith 60 holes and PEG400 as spin finish are shown in Table 6.

TABLE 6 Mechanical properties of 60 Filament Oriented P4HB MultifilamentProduced with PEG400 as Spin Finish Denier per Break # Total filamentTenacity Elongation Specimen # Filaments Denier (dpf) (gpd) (%) 1 60 1191.98 6.725 24.5 2 60 119 1.98 6.619 24.0 3 60 119 1.98 6.524 25.5Average 60 119 1.98 6.622 24.7

Example 2 Preparation of Multifilament P4HB Braided Sutures and KnittedTubes

Oriented 60-filament yarns produced according to Example 1 with thefollowing spin finishes were processed into P4HB braided sutures: Tween®20, PEG400, PEG Stearate, and Dacospin®. The mechanical properties ofthe braids produced are shown in Table 7.

TABLE 7 Mechanical properties of P4HB braided sutures produced withdifferent spin finishes Avg. Spin Diameter Lot # Finish (nm) Denier Load(kfg) 09X0505-5 50% Tween 0.722 5737.3 21.0 09X0513-4 50% PEG 400 0.6715328.7 22.0 09X0513-7 15% PEG Stearate 0.781 5047.4 21.3 09X0519-2  5%Dacospin 0.727 5021.7 20.8 Tenacity Strength Break Lot # (gpd) (kfg/mm²)Elong. (%) 09X0505-5 3.66 3.21 40.5 09X0513-4 4.13 3.89 40.3 09X0513-74.22 2.78 42.2 09X0519-2 4.14 3.13 42.8

Oriented 60-filament yarn produced according to Example 1 with thefollowing spin finishes were also processed into P4HB circular knittedtubes using a single feed, circular weft knitting machine (Lamb KnittingCo., model ST3A/ZA): Tween 20, PEG400, PEG40 Stearate, Dacospin, andFilapan. The width of the flat tube was approximately 9 mm.

Various additional P4HB braid configurations produced using PEG400 werealso prepared as indicated in Table 8, and characterized.

TABLE 8 Mechanical properties of various P4HB braid configurationsprepared using PEG400 Avg. Example # # Carriers TPI PPI # Core Diameter1 16 2 45 5 multi 0.566 2 16 2 45 6 multi 0.559 3 2 ply 16 2 N/A 3 multi0.808 4 16 2 30 3 multi 0.417 5 16 2 40 3 multi 0.504 6 16 2 50 3 multi.0495 7 16 2 60 3 multi 0.563 8 16 2 75 3 multi 0.577 9  8 2 75 1 multi0.405 10 16 2 75 3 multi 0.587 11  8 2 75 1 multi 0.412 12 16 2 N/A 12multi  0.712 13 16 2 70 16 multi  0.742 14 2 ply 12 2 70 5 multi N/ABreak Load Tenacity Elong. Example # Denier (kfg) (gpd) (%) 1 306516.519 5.39 38.9 2 2883 16.262 5.64 38.4 3 5328.7 22.00 4.13 40.3 4 246214.83 6.02 32.7 5 2520 14.341 5.69 34.9 6 2605 14.226 5.46 39.8 7 260813.50 5.18 40.9 8 3042 12.58 4.14 39.2 9 1527 4.86 3.18 42.8 10 269912.00 4.45 42.5 11 1349 4.52 3.35 50.6 12 N/A 17.045 N/A 50.9 13 N/A19.185 N/A 53.6 14 N/A 16.11 N/A 46 All multifilament used is 120denier.

Example 3 Scouring of P4HB Multifilament

P4HB knitted circular tubes prepared as described in Example 2 werescoured for 24 hours with 70% aqueous ethanol. All scouring was done at37° C. in a shaker (50 rpm) in 50 mL plastic Falcon® tubes containing 50mL of wash solution. Following this treatment, the scoured P4HB knittedtubes (2 gram samples) were tested for cytotoxicity according to theprotocol described in Example 4.

Example 4 Cytotoxicity Testing of P4HB Multifilament after Scouring

To test the cytotoxicity of the spin finishes, twice the amount of spinfinish residue present on the circular knitted tube after 24 hourwashing with 70% ethanol (see Example 3) was determined (by GC forDacospin®, Tween 20, and PEG20 Stearate, and by GPC-HPLC for PEG400) andsupplied in a vial for testing (based on a 2 g sample mass of tube). Theamounts used for preparing the cytotoxicity samples are shown in Table9.

Cytotoxicity testing was undertaken using the ISO Elution Method (1×MEMExtract) following the guidelines of the International Organization forStandardization 10993: Biological Evaluation of Medical Devices, Part 5:Tests for Cytotoxicity: in vitro Methods.

TABLE 9 Results of cytotoxicity testing of Spin Finishes Scour 2X MassResults Residual Wt Residual Cytotoxicity Spin Finish Wt % Wt % Ratio mgResult Tween ® 20 0.60 1.20 0.012 24 Fail PEG40Stearate 0.12 0.24 0.00244.8 Fail PEG400 0.30 0.60 0.006 12 Pass DacoSpin ® 0.07 0.14 0.0014 2.8Fail

Additionally, 2 g of the knitted tube itself after 10 minute ethanolwashing, was submitted for cytotoxicity testing. Results for the washed,knitted tubes are shown in Table 10.

TABLE 10 Results for cytotoxicity testing of 2 g of P4HB multifilamentafter 10 minute ethanol wash*. Residual Wt Calculated ResidualCytotoxicity Spin Finish Wt % Ratio Mass (mg) Result Tween ® 20 1.650.017 33 Fail PEG40Stearate 0.52 0.005 10.4 Pass PEG400 0.77 0.008 15.4Pass DacoSpin ® 0.67 0.007 13.4 Fail *The Filapan spin finish coated onthe knitted tube also failed this cytotoxicity test

As shown in Table 10, only the PEG400 spin finish passed thecytotoxicity testing at twice the level present after 24 hours ofethanol washing, and as a residue on an actual knitted sample of P4HBmultifilament after a 10 minute ethanol wash. PEG40 Stearate passedcytotoxicity testing as a residue on the washed mesh, but both Tween® 20and Dacospin® failed both of these cytotoxicity tests.

Example 5 Braided P4HB Suture Comprising an Outer Multifilament Sheathand an Inner P4HB Monofilament Core

P4HB multifilament fiber (120 denier), comprising two 60-filament yarnsproduced as described in Example 1, was placed on 16 carrier bobbins. Asize 1 P4HB monofilament fiber (produced as described by the method inExample 7) was fed into the braider core eyelet and run at 70 picks perinch (PPI) to produce a P4HB braided suture comprising an outermultifilament sheath of P4HB, and an inner P4HB monofilament core withthe properties described in Table 11.

TABLE 11 Properties of a braided P4HB suture with an outer multifilamentsheath and an inner P4HB monofilament core Avg. Example # # Carriers TPIPPI # Core Diameter 1 16 2 70 1 mono size 1 0.743 Load Tenacity Example# Denier (kfg) (gpd) Break Elong. (%) 1 N/A 26.654 N/A 46.4 Allmultifilament used is 120 denier.

Example 6 Braided P4HB Suture Comprising an Outer Multifilament andMonofilament Sheath and an Inner P4HB Monofilament Core

P4HB multifilament fiber (120 denier), produced as described in Example1, was placed on 8 of 16 carrier bobbins. The remaining 8 bobbins werefilled with size 5/0 P4HB monofilament fiber (produced as described bythe method in Example 7). A bundle of 3 ply size 5/0 P4HB monofilamentfiber was fed into the braider core eyelet, and run at 70 picks per inchto produce a P4HB braided suture comprising an outer multifilament andmonofilament sheath of P4HB, and an inner P4HB monofilament 3-ply corewith the properties described in Table 12.

TABLE 12 Properties of a braided P4HB suture with an outer multifilamentsheath and an inner P4HB monofilament core # Mono # Multi Example #Carriers Carriers TPI PPI # Core 1 8 mono 8 multi 2 70 3 ply size 5/0size 5/0 mono Example # Avg. Diameter Denier Load (kfg) Tenacity (gpd) 1N/A N/A N/A N/A All multifilament used is 120 denier.

Example 7 Preparation of P4HB Monofilament by Melt Extrusion

Bulk P4HB resin in pellet form was dried to under 300 ppm water using arotary vane vacuum pump system. The dried resin was transferred to anextruder feed hopper with nitrogen purge to keep the pellets dry. Thepellets were gravity fed into a chilled feeder section and introducedinto the extruder barrel, which was 1.50 inches in diameter and fittedwith an extrusion screw with a 30:1 L/D ratio. The extruder barrelcontained 5 heating zones (or extrusion zones)—zones 1, 2, 3, 4 and 5,and was manufactured by American Kuhne. The heated and softened resinfrom the extruder was fed into a heated metering pump (melt pump) andfrom the melt pump the extruded resin was fed into the heated block andan eight hole spinneret assembly. Processing profile ranges from 40° C.to 260° C. for temperatures, and 400 psi to 2000 psi for pressures, wereused. The molten filaments were water quenched and conveyed into athree-stage orientation, with inline relaxation, before winding of themonofilaments on spools. Test values for extruded monofilament fiber areshown in Table 13.

TABLE 13 Mechanical Test Data for P4HB Monofilament Fiber BreakingStrength, Fiber USP Size Diameter, mm Kg Break Elongation 5/0 0.150 1.8030% 6/0 0.100 1.00 29%

Example 8 Preparation of a P4HB Monofilament Mesh with Tween® 20

Spools with P4HB monofilament fiber prepared as described in Example 7were converted into Tween® 20 coated P4HB monofilament mesh as follows:Monofilament fibers from 49 spools were pulled under uniform tension tothe surface of a warp beam. A warp is a large wide spool onto whichindividual fibers are wound in parallel to provide a sheet of fibersready for coating with a 10% solution of Tween® 20 lubricant. Tween® 20lubricant was added to the surface of the sheet of fiber by means of a‘kiss’ roller that was spinning and was immersed in a bath filled withTween® 20. The upper surface of the roller was brought into contact withthe sheet of fiber, and the roller spun at a uniform speed to provide aconsistent application of Tween® 20 finish. Following the application ofTween® 20, the sheet of fiber was placed onto a creel position such thateach spooled fiber was aligned and wrapped side by side to the nextspooled fiber on a warp beam. Next, warp beams were converted into afinished mesh fabric by means of interlocking knit loops. Eight warpbeams were mounted in parallel onto a tricot machine let-offs and fedinto the knitting elements at a constant rate determined by the ‘runnerlength’. Each individual monofilament fiber from each beam was fedthrough a series of dynamic tension elements down into the knitting‘guides’. Each fiber was passed through a single guide, which was fixedto a guide bar. The guide bar directed the fibers around the needlesforming the mesh fabric structure. The mesh fabric was then pulled offthe needles by the take down rollers at a constant rate of speeddetermined by the fabric ‘quality’. The mesh fabric was then taken upand wound onto a roll ready for finished product inspection.

Example 9 Scouring of P4HB Monofilament Mesh and Cytotoxicity Testing

The P4HB monofilament mesh produced according to the method of Example 8was scored ultrasonically with water, heat set in hot water, and thenwashed with a 70% aqueous ethanol solution. Cytotoxicity testing of twograms of the mesh was undertaken using the ISO Elution Method (1×MEMExtract) following the guidelines of the International Organization forStandardization 10993: Biological Evaluation of Medical Devices, Part 5:Tests for Cytotoxicity: in vitro Methods. The scoured P4HB monofilamentmesh passed the cytotoxicity testing. The content of Tween 20 prior toscouring was approximately 0.3 wt %, and at this level the mesh failedthe cytotoxicity testing. The residual content of Tween 20 afterscouring was approximately 0.03 wt %, and at this level the mesh passedthe cytotoxicity testing.

Example 10 Coating of P4HB Braided Sutures with Spin Finish

Braided P4HB sutures prepared according to Example 2, and scoured by themethod of Example 3, can be recoated with PEG400. Cytotoxicity testingof a braided P4HB suture coated with approximately 6 wt % PEG400 wasundertaken using the ISO Elution Method (1×MEM Extract) following theguidelines of the International Organization for Standardization 10993:Biological Evaluation of Medical Devices, Part 5: Tests forCytotoxicity: in vitro Methods. The PEG400 braided suture passed thecytotoxicity testing at this coating weight.

Example 11 Preparation of Hybrid P4HB/Polypropylene Meshes

Spools with P4HB monofilament fiber prepared as described in Example 7were converted into Tween® 20 coated P4HB monofilament mesh as follows.Monofilament fibers from 49 spools were pulled under uniform tension tothe surface of a warp beam. A warp is a large wide spool onto whichindividual fibers are wound in parallel to provide a sheet of fibersready for coating with a 10% solution of Tween® 20 lubricant. Tween® 20lubricant was added to the surface of the sheet of fiber by means of a‘kiss’ roller that was spinning and was immersed in a bath filled withTween® 20. The upper surface of the roller was brought into contact withthe sheet of fiber, and the roller spun at a uniform speed to provide aconsistent application of Tween® 20 finish. Following the application ofTween® 20, the sheet of P4HB fibers was placed onto a creel positionsuch that each spooled fiber was aligned and wrapped side by side to thenext spooled fiber to form a set of P4HB warp beams. Similarly 49 spoolsof polypropylene monofilament, with diameter similar to P4HBmonofilament, were processed to form a set of polypropylene warp beams.Next, warp beams were converted into a finished mesh fabric by means ofinterlocking knit loops. Each set of warp beams was mounted in parallelonto a tricot machine on two separate let-offs and each set of beams wasthreaded into a separate guide bar for feeding into the knittingneedles. The P4HB warp beam fiber was fed to the front guide bar and thepolypropylene warp beam fiber was fed to the back guide bar. Eachindividual monofilament fiber from each beam was fed through a series ofdynamic tension elements down into the knitting ‘guides’. The guide barsdirected the fibers around the needles forming the mesh fabricstructure. Knitting patterns were selected so that intact polypropyleneknits would remain once the absorbable P4HB monofilament was degradedfrom the construction in vivo. Both materials (P4HB and polypropylene)were knitted together to form one knitted construction. The mesh fabricwas then pulled off the needles by the take down rollers at a constantrate of speed determined by the fabric ‘quality’. The hybrid mesh fabricwas then taken up and wound onto a roll.

The P4HB filaments were then dissolved away by immersing the hybrid meshin chloroform. Examples of hybrid meshes prepared with two differentsizes of monofilament, and two ratios of polypropylene (PP) to P4HB arelisted in Table 14.

TABLE 14 Hybrid Mesh Prepared from Polypropylene (PP) and P4HBIdentification Mesh Description SN 3528 75% PP, 25% P4HB; Tepha Lot #902001; filament diameter—100 μm SN 3566 75% PP, 25% P4HB; Tepha Lot #902003; filament diameter—150 μm SN 3529 50% PP, 50% P4HB; Tepha Lot #902002; filament diameter—100 μm SN 3567 50% PP, 50% P4HB; Tepha Lot #902004; filament diameter—150 μm

To demonstrate that the hybrid meshes listed in Table 14 wouldprogressively lose burst strength after implantation in vivo, samples ofeach mesh (n=5 for each time point, 2 inch×2 inch squares) were placedin 3M HCl at 37° C. for 5, 24 and 48 hours prior to being subjected tomesh burst strength testing. Mesh Burst testing was performed at therequired time points according to ASTM D6797-02 (Standard Test Methodfor Bursting Strength of Fabrics Constant-Rate-of-Extension (CRE) BallBurst Test) at ambient conditions. The ball burst fixture had a 1.6 cmcircular opening and a 1 cm diameter half-rounded probe. Molecularweight measurements were made by placing hybrid mesh in chloroform todissolve P4HB filament, and then determining molecular weights (Mw) byGPC. Over the course of the study, it became evident which filamentswithin the mesh were P4HB and which were polypropylene. By the 48 hrtime point, the P4HB filaments were opaque white in color, and many werecrumbling from the mesh. The polypropylene filaments did not appear tochange over time. Test data for the samples shown in Table 14 at eachtime point, including time t=0, is shown in Tables 15-18.

TABLE 15 Burst Strength and Mw testing data for SN 3528 Hybrid Meshsamples - In Vitro testing Peak Incubation Avg. thick Thickness PeakLoad Load Time (hr) (mm) Std Dev (KgF) Std Dev  0 0.374 0.021 5.9330.727  5 0.339 0.014 5.277 0.431 24 0.355 0.032 5.263 0.954 48 0.3260.007 6.025 0.576 Extension at Extension at Incubation Peak Load PeakLoad % Strength Mw % Mw Time (hr) (mm) Std Dev Retention (Da) Retention 0 5.967 0.236 100 266,830 100.0  5 6.875 0.362 88.9 209,900 78.7 246.556 0.382 88.7 111,480 41.8 48 5.363 0.545 101.6  64,816 24.3

TABLE 16 Burst Strength and Mw testing data for SN 3566 Hybrid Meshsamples - In Vitro testing Peak Incubation Avg. thick Thickness PeakLoad Load Time (hr) (mm) Std Dev (KgF) Std Dev  0 0.863 0.011 14.3191.139  5 0.861 0.012 10.465 1.211 24 0.870 0.008 10.684 1.214 48 0.8600.012 11.648 1.163 Extension at Extension at Incubation Peak Load PeakLoad % Strength Mw % Mw Time (hr) (mm) Std Dev Retention (Da) Retention 0 8.142 0.274 100 310,260 100.0  5 9.634 0.653 73.1 245,390 79.1 2410.283 0.419 74.6 127,270 41.0 48 10.516 0.501 81.3  73,388 23.7

TABLE 17 Burst Strength and Mw testing data for SN 3529 Hybrid Meshsamples - In Vitro testing Avg. Peak Incubation thickness Thickness PeakLoad Load Time (hr) (mm) Std Dev (KgF) Std Dev  0 0.485 0.018 11.4430.553  5 0.456 0.010 8.940 0.574 24 0.472 0.023 7.380 0.886 48 0.4620.018 7.704 1.045 Extension at Extension at Incubation Peak Load PeakLoad % Strength Mw % Mw Time (hr) (mm) Std Dev Retention (Da) Retention 0 5.563 0.286 100 256,990 100.0  5 4.983 0.128 78.1 207,520 80.8 245.256 0.354 64.5 114,390 44.5 48 5.698 0.363 67.3  71,319 27.8

Example 12 Preparation of a Collagen Coated PHA Device

A monofilament P4HB mesh prepared as described in Example 8 can becoated with collagen by immersion into an aqueous slurry of 2% bovineskin collagen (prepared according to Example 1 of U.S. Pat. No.5,108,424 to Hoffman et al). The slurry includes 8% glycerol and 17%ethanol. The coated mesh is removed from the slurry, and allowed to dryfor approximately 30 mins at room temperature. The coating and dryingsteps are repeated three more times to yield a collagen coated P4HBmonofilament mesh.

TABLE 18 Burst Strength and Mw testing data for SN 3567 Hybrid Meshsamples - In Vitro testing Peak Incubation Avg. thick Thickness PeakLoad Load Time (hr) (mm) Std Dev (KgF) Std Dev  0 0.768 0.032 32.4283.110  5 0.817 0.018 23.954 1.217 24 0.814 0.009 15.621 1.591 48 0.8200.014 16.498 1.842 Extension at Extension at Incubation Peak Load PeakLoad % Strength Mw % Mw Time (hr) (mm) Std Dev Retention (Da) Retention 0 8.747 0.708 100 302,670 100.0  5 7.665 0.122 73.9 235,550 77.8 247.484 0.297 48.2 120,880 39.9 48 8.194 0.487 50.9  77,384 25.6

Example 13 Crosslinking of a Collagen Coated PHA Monofilament Mesh

The coated mesh prepared in Example 12 can be crosslinked by exposure toformaldehyde vapor for five minutes. The resulting composite is thenallowed to dry for approximately 15 mins in air at room temperature, andis then vacuum dried to remove residual crosslinking agent and anymoisture.

Example 14 Tissue Drag of Scoured TephaFLEX Braid

A 16-carrier, single-ply braided suture over a 6-ply core was preparedfrom 60-filament TephaFLEX yarn using PEG400 as a spin finish. The braidwas then scoured in water for various lengths of time to remove thePEG400.

The amount of force required to pull the suture through tissue wasdetermined using a tissue drag test. In this test, the suture is passedthrough a simulated tissue multiple times, and one of the free ends isfixed to the movable grip of a universal testing machine. The simulatedtissue is held stationary in a frame below the movable cross member. Thetest is initiated and the kilograms of force (Kgf) required to pull thesuture through the simulated tissue is recorded. The suture may betested dry or after wetting in water. Results for the 16-carrier over6-ply core braided TephaFLEX suture are show in Table 19. Comparison ismade to a Vicryl control suture. As can be seen in Table 19, the10-minute scoured TephaFLEX braid compares well to the Vicryl braid inthat the drag forces are similar. However, as the time of scouringincreases, and the amount of residual PEG400 decreases, the drag forceincreases.

TABLE 19 Drag force measurements for TephaFLEX braid. Avg Drag ForcePeak Load Sample Description (Kgf) (Kgf) Vicryl 0.338 0.358 Size 2 Lot #CDM945, wet TephaFLEX Lot # 100136 0.323 0.373 Size 2, 10 min scouredsterile, wet TephaFLEX Lot # 100198 0.415 0.475 Size 2, 2 hours scouredsterile, wet

Example 15 Tissue Drag of PEG2000 Coated TephaFLEX Braids

A 15-minute scoured TephaFLEX braid of Example 14 was coated with aPEG2000 coating to reduce the amount of tissue drag. PEG2000 wasdissolved in ethanol (30% wt./vol.) and the braided suture was pulledthrough a bead of the solution to thoroughly wet the braid. The braidwas allowed to dry to leave behind a residue of PEG2000 at a coatingweight of approximately 7% by wt. The tissue drag of the coated sutureafter wetting in water was performed as described in Example 14, and theresults are shown in Table 20.

TABLE 20 Drag force measurements for TephaFLEX braid coated with PEG2000compared to Vicryl and uncoated TephaFLEX controls. Avg Drag Peak AvgDrag Force, Peak Load, Force Load Relative to Relative to Specimen Name(kgf) (kgf) Vicryl (%) Vicryl (%) Vicryl Control 0.319 0.344 N/A N/AScoured 0.284 0.299 89% 87% TephaFLEX Control PEG2000 Coated 0.242 0.28876% 84% TephaFLEX Braid

As can be seen in the table, the drag force of the coated suture islower than that of the uncoated TephaFLEX and Vicryl controls, thusdemonstrating that the PEG2000 coating is effective at reducing thetissue drag of the braided suture.

Example 16 Tissue Drag of PVA Coated TephaFLEX Braids

A 15-minute scoured TephaFLEX braid of example 14 was coated with apolyvinyl alcohol (PVA) coating to reduce the amount of tissue drag. PVAwas dissolved in water at 8% and the braided suture was pulled through abead of the solution to thoroughly wet the braid. The braid was allowedto dry to leave behind a residue of PVA at a coating weight ofapproximately 3% by wt. The tissue drag of the coated suture afterwetting in water was performed as described in Example 14, and theresults are shown in Table 21. As can be seen in the table, the dragforce of the PVA-coated suture is substantially lower than that of theuncoated TephaFLEX and Vicryl controls, thus demonstrating that the PVAcoating is effective at reducing the tissue drag of the braided suture.

TABLE 21 Drag force measurements for TephaFLEX braid coated with PVAcompared to Vicryl and uncoated TephaFLEX controls. Relative to VicrylAvg Drag Peak Load Avg Drag Peak Load Specimen Name Force (kgf) (kgf)Force (%) (%) Vicryl 0.316 0.337 N/A N/A Control Scoured TephaFLEX 0.3050.346 97% 103% Control PVA Coated 0.173 0.202 55%  60% TephaFLEX Braid

Modifications and variations of the invention described herein will beobvious to those skilled in the art and are intended to come within thescope of the appended claims.

We claim:
 1. A medical device comprising a polymeric multifilament yarn,wherein the polymer consists of a polyhydroxyalkanoate, wherein thedenier per filament is less than 4.0, and the multifilament yarn has atenacity greater than 6.1 grams per denier.
 2. The device of claim 1,wherein the device is selected from the group consisting of barbedsutures, braided sutures, ligatures, hybrid sutures of monofilament andmultifilament fibers, braids, knitted or woven meshes, monofilamentmeshes, multifilament meshes, knitted tubes, stents, stent grafts, drugdelivery devices, devices for temporary wound or tissue support, devicesfor soft tissue repair, devices for replacement or regeneration, repairpatches, tissue engineering scaffolds, retention membranes,anti-adhesion membranes, tissue separation membranes, hernia repairdevices, breast reconstruction devices, devices for blepharoplasty,devices for facial scar revisions, devices for forehead lifts, devicesfor mentoplasty, devices for malar augmentation, devices for otoplasty,devices for rhinoplasty, devices for neck lift surgery, devices forrhytidectomy, threadlift devices to lift and support sagging areas ofthe face, brow, and neck, fixation devices, cardiovascular patches,vascular closure devices, vascular grafts, slings, biocompatiblecoatings, rotator cuff repair devices, meniscus repair devices, adhesionbarriers, guided tissue repair/regeneration devices, articular cartilagerepair devices, nerve guides, tendon repair devices, ligament repairdevices, intracardiac septal defect repair devices, left atrialappendage (LAA) closure devices, pericardial patches, bulking andfilling agents, vein valves, heart valves, bone marrow scaffolds,meniscus regeneration devices, ligament and tendon graft, ocular cellimplants, spinal fusion devices, imaging devices, skin substitutes,dural substitutes, bone graft substitutes, wound dressings, andhemostats.
 3. The device of claim 2, wherein the breast reconstructiondevice is selected from the group consisting of devices for breastaugmentation, devices for mastopexy, devices for breast reduction,devices for breast positioning and shaping, and devices for breastreconstruction following mastectomy.
 4. The device of claim 2,comprising a braided suture wherein the suture comprises an outerpolyhydroxyalkanoate multifilament sheath and an innerpolyhydroxyalkanoate monofilament core.
 5. The device of claim 4,comprising a suture wherein the suture comprises an outerpolyhydroxyalkanoate multifilament and monofilament sheath, and an innerpolyhydroxyalkanoate monofilament core.
 6. The device of claim 4,wherein the polyhydroxyalkanoate comprises 4-hydroxybutyrate.
 7. Thedevice of claim 4, wherein the inner monofilament core is barbed, or ismade from a non-degradable polymer.
 8. The device of claim 1, whereinthe device comprises one or more additional components selected from thegroup consisting of plasticizers, nucleants, collagen, crosslinkedcollagen, blends or copolymers of polyhydroxyalkanoates, blends orcopolymers of lactic acid, glycolic acid, caprolactone, p-dioxanone, ortrimethylene carbonate, polymer additives, dyes, compatibilizers,fillers, therapeutic agents, diagnostic agents, and prophylactic agents.9. The device of claim 1, wherein the device is a suture and contains atleast one or more fibers with contrasting dye to provide an identifiablecolor trace in the suture strand.
 10. The device of claim 1, wherein thedevice is a suture used for ligament and tendon repair.
 11. The deviceof claim 1, wherein the device is a surgical mesh.
 12. The device ofclaim 11, wherein the surgical mesh comprises polyhydroxyalkanoate fiberand a permanent fiber.
 13. The device of claim 12, wherein the permanentfiber is polypropylene, a polyester, or a combination thereof.
 14. Thedevice of claim 11, wherein the surgical mesh comprises monofilamentfibers.
 15. The device of claim 11, wherein the surgical mesh has beencoated or encapsulated with collagen.
 16. The device of claim 15,wherein the porosity of the collagen is at least 5 μm in diameter. 17.The device of claim 15, wherein the polyhydroxyalkanoate component is,coated or encapsulated with collagen, the collagen is crosslinked, andthe device is sterilized with ethylene oxide or by irradiation.
 18. Amethod comprising implanting or administering a medical device at a sitein or on a patient in need thereof, wherein the medical device comprisesa polymeric multifilament yarn, wherein the polymer consists of apolyhydroxyalkanoate, and wherein the denier per filament is less than4.0 and the multifilament yarn has a tenacity greater than 6.1 grams perdenier and wherein the medical device is selected from the groupconsisting of barbed sutures, braided sutures, ligatures, hybrid suturesof monofilament and multifilament fibers, braids, knitted or wovenmeshes, monofilament meshes, multifilament meshes, knitted tubes,stents, stent grafts, drug delivery devices, devices for temporary woundor tissue support, devices for soft tissue repair, devices forreplacement or regeneration, repair patches, tissue engineeringscaffolds, retention membranes, anti-adhesion membranes, tissueseparation membranes, hernia repair devices, breast reconstructiondevices, devices for blepharoplasty, devices for facial scar revisions,devices for forehead lifts, devices for mentoplasty, devices for malaraugmentation, devices for otoplasty, devices for rhinoplasty, devicesfor neck lift surgery, devices for rhytidectomy, threadlift devices tolift and support sagging areas of the face, brow, and neck, fixationdevices, cardiovascular patches, vascular closure devices, vasculargrafts, slings, biocompatible coatings, rotator cuff repair devices,meniscus repair devices, adhesion barriers, guided tissuerepair/regeneration devices, articular cartilage repair devices, nerveguides, tendon repair devices, ligament repair devices, intracardiacseptal defect repair devices, left atrial appendage (LAA) closuredevices, pericardial patches, bulking and filling agents, vein valves,heart valves, bone marrow scaffolds, meniscus regeneration devices,ligament and tendon graft, ocular cell implants, spinal fusion devices,imaging devices, skin substitutes, dural substitutes, bone graftsubstitutes, wound dressings, and hemostats, wherein the breastreconstruction device is selected from the group consisting of devicesfor breast augmentation, devices for mastopexy, devices for breastreduction, devices for breast positioning and shaping, and devices forbreast reconstruction following mastectomy.
 19. The device of claim 1,wherein the filaments are derived by melt-extrusion processing of thepolyhydroxyalkanoate polymer between 40° C. and 275° C., allowing thepolymer to cool and solidify and applying polymers or oligomers ofethylene oxide or propylene oxide polyethylene glycol sorbitanmonolaurate to the filaments or yarn by passage through a spin finishapplicator either inline or offline.
 20. The device of claim 19, whereinthe multifilament yarn is coated with a coating material selected fromthe group consisting of polymers or oligomers of ethylene oxide,polymers or oligomers of propylene oxide, polyvinyl alcohol, andcombinations thereof.
 21. The device of claim 1, wherein thepolyhydroxyalkanoate has a molecular weight between 50,000 and 1,200,000measured by gel permeation chromatography.
 22. The device of claim 20,wherein the polyhydroxyalkanoate comprises 4-hydroxybutyrate.
 23. Thedevice of claim 20, wherein the coating material is polyethylene glycolhaving an average molecular weight of 1000 to 10,000 daltons.
 24. Thedevice of claim 20, wherein the coating material is polyvinyl alcohol.25. The device of claim 20, wherein the average tissue drag force of thecoated braid is reduced at least 10% relative to the uncoated braid. 26.A medical device comprising an oriented polyhydroxyalkanoatemultifilament yarn, wherein the denier per filament is less than 4.0,and the multifilament yarn has a tenacity greater than 6.1 grams perdenier.
 27. The device of claim 21, wherein the coating material ispolyethylene glycol sorbitan monolaurate.
 28. The device of claim 19,wherein the polymer is polyethylene glycol having an average molecularweight of 100 to 1000 daltons in a spin finish.
 29. The device of claim17, treated with plasma gas prior to coating or encapsulating withcollagen.